Hemodynamic wall shear stress profiles influence the magnitude and pattern of stenosis in a pig AV fistula

Krishnamoorthy, Mahesh; Banerjee, Rupak K.; Wang, Yan; Zhang, Jianhua; Roy, Abhijit Sinha; Khoury, Saeb F.; Arend, Lois J.; Rudich, Steven; Roy‐Chaudhury, Prabir

doi:10.1038/ki.2008.379

Cited by 90 publications

(103 citation statements)

References 26 publications

(29 reference statements)

Supporting

Mentioning

101

Contrasting

Unclassified

Order By: Relevance

“…Magnetic resonance imaging and computed tomography have been used in both large-animal and clinical studies to evaluate neointimal hyperplasia development, lumen geometry, hemodynamics, and computational fluid dynamics (34,(64)(65)(66). These imaging technologies would be even more powerful if they could be applied in transgenic rodent models where the combination of pathobiology and computational fluid dynamics modeling could be studied in greater depth.…”

Section: Novel Technologies and Strategies To Unravel Vascular Accessmentioning

confidence: 99%

New Insights into Dialysis Vascular Access: Molecular Targets in Arteriovenous Fistula and Arteriovenous Graft Failure and Their Potential to Improve Vascular Access Outcomes

Lee

Misra

2016

CJASN

View full text Add to dashboard Cite

Vascular access dysfunction remains a major cause of morbidity and mortality in hemodialysis patients. At present there are few effective therapies for this clinical problem. The poor understanding of the pathobiology that leads to arteriovenous fistula (AVF) and graft (AVG) dysfunction remains a critical barrier to development of novel and effective therapies. However, in recent years we have made substantial progress in our understanding of the mechanisms of vascular access dysfunction. This article presents recent advances and new insights into the pathobiology of AVF and AVG dysfunction and highlights potential therapeutic targets to improve vascular access outcomes.

show abstract

Section: Novel Technologies and Strategies To Unravel Vascular Accessmentioning

confidence: 99%

New Insights into Dialysis Vascular Access: Molecular Targets in Arteriovenous Fistula and Arteriovenous Graft Failure and Their Potential to Improve Vascular Access Outcomes

Lee

Misra

2016

CJASN

View full text Add to dashboard Cite

show abstract

“…However, AVFs in hemodialysis patients are usually constructed by anatomizing the end of a vein to the side of an artery. The exact configuration of the AVF is a crucial characteristic of an AV access model since it determines the hemodynamic profile within the conduit 4 . The latter is an important contributor to endothelial dysfunction and subsequent development of intimal hyperplasia (IH) 5 .…”

Section: Introductionmentioning

confidence: 99%

A Novel Murine Model of Arteriovenous Fistula Failure: The Surgical Procedure in Detail

Wong

Vries

Wang

et al. 2016

JoVE

Self Cite

View full text Add to dashboard Cite

The arteriovenous fistula (AVF) still suffers from a high number of failures caused by insufficient remodeling and intimal hyperplasia from which the exact pathophysiology remains unknown. In order to unravel the pathophysiology a murine model of AVF-failure was developed in which the configuration of the anastomosis resembles the preferred situation in the clinical setting. A model was described in which an AVF is created by connecting the venous end of the branch of the external jugular vein to the side of the common carotid artery using interrupted sutures. At a histological level, we observed progressive stenotic intimal lesions in the venous outflow tract that is also seen in failed human AVFs. Although this procedure can be technically challenging due to the small dimensions of the animal, we were able to achieve a surgical success rate of 97% after sufficient training. The key advantage of a murine model is the availability of transgenic animals. In view of the different proposed mechanisms that are responsible for AVF failure, disabling genes that might play a role in vascular remodeling can help us to unravel the complex pathophysiology of AVF failure. Video LinkThe video component of this article can be found at

show abstract

“…These include vein configuration (22), hemodynamics stress (39), inflammation (20), and preexisting diseases like diabetes (40) and kidney failure (26). The above conditions induce de novo accumulation of growth factors such as VEGF (48), plateletderived growth factor (41), fibroblast growth factor (42), and transforming growth factor-␤ (18) and their receptor tyrosine kinases (RTKs) in the outflow vein, which ultimately increase the proliferation, migration, and survival of neointimal cells and the subsequent thickening of the vessel wall.…”

mentioning

confidence: 99%

c-Kit signaling determines neointimal hyperplasia in arteriovenous fistulae

Skartsis

Martinez

Duque

et al. 2014

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

Skartsis N, Martinez L, Duque JC, Tabbara M, Velazquez OC, Asif A, Andreopoulos F, Salman LH, Vazquez-Padron RI. c-Kit signaling determines neointimal hyperplasia in arteriovenous fistulae. Am J Physiol Renal Physiol 307: F1095-F1104, 2014. First published September 3, 2014 doi:10.1152/ajprenal.00292.2014.-Stenosis of arteriovenous (A-V) fistulae secondary to neointimal hyperplasia (NIH) compromises dialysis delivery, which worsens patients' quality of life and increases medical costs associated with the maintenance of vascular accesses. In the present study, we evaluated the role of the receptor tyrosine kinase c-Kit in A-V fistula neointima formation. Initially, c-Kit was found in the neointima and adventitia of human brachiobasilic fistulae, whereas it was barely detectable in control veins harvested at the time of access creation. Using the rat A-V fistula model to study venous vascular remodeling, we analyzed the spatial and temporal pattern of c-Kit expression in the fistula wall. Interestingly, c-Kit immunoreactivity increased with time after anastomosis, which concurred with the accumulation of cells in the venous intima. In addition, c-Kit expression in A-V fistulae was positively altered by chronic kidney failure conditions. Both blockade of c-Kit with imatinib mesylate (Gleevec) and inhibition of stem cell factor production with a specific short hairpin RNA prevented NIH in the outflow vein of experimental fistulae. In agreement with these data, impaired c-Kit activity compromised the development of NIH in A-V fistulae created in c-Kit W/Wv mutant mice. These results suggest that targeting of the c-Kit signaling pathway may be an effective approach to prevent postoperative NIH in A-V fistulae. arteriovenous fistula; hemodialysis; neointima THE ARTERIOVENOUS (A-V) fistula is the preferred type of vascular access for hemodialysis patients (29). It achieves higher patency rates, has fewer complications than synthetic grafts (12,29,31), and has a lower risk of infections than central venous catheters (17,29). Despite its advantages, A-V fistulae frequently fail to mature or become dysfunctional after successful dialysis sessions, and this occurs primarily due to the development of neointimal hyperplasia (NIH) within the A-V fistula circuit (2, 5, 39). Stenosed A-V fistulae can sometimes be salvaged through angioplasty or surgical interventions, but these attempts often result in restenosis or additional complications (32). Therefore, there is an unmet medical need for treatments that prevent NIH and improve A-V fistula function. To this end, it is necessary to better define the factors underlying the pathological remodeling of the A-V fistula wall.A-V fistula maturation is a dynamic vascular process with multiple factors contributing to the development of NIH. These include vein configuration (22) In the present study, we investigated the role of c-Kit in the pathological remodeling of A-V fistulae. We show that activation of the c-Kit signaling pathway in adventitial and neointimal cells precedes arteri...

show abstract

Hemodynamic wall shear stress profiles influence the magnitude and pattern of stenosis in a pig AV fistula

Cited by 90 publications

References 26 publications

New Insights into Dialysis Vascular Access: Molecular Targets in Arteriovenous Fistula and Arteriovenous Graft Failure and Their Potential to Improve Vascular Access Outcomes

New Insights into Dialysis Vascular Access: Molecular Targets in Arteriovenous Fistula and Arteriovenous Graft Failure and Their Potential to Improve Vascular Access Outcomes

A Novel Murine Model of Arteriovenous Fistula Failure: The Surgical Procedure in Detail

c-Kit signaling determines neointimal hyperplasia in arteriovenous fistulae

Contact Info

Product

Resources

About